Advanced Patient-derived 3D Bone Organoids for In Vitro Osteoporosis Research

Fragility fractures are among the most serious consequences of impaired skeletal health in older adults, often leading to reduced mobility, loss of independence, and long-term disability. Although current standards of care provide important tools for assessing skeletal health and fracture risk, patient-specific biological responses to altered bone remodelling, mechanical loading, and inflammation remain difficult to capture in conventional assessment workflows. This is particularly relevant in osteoporosis and related age-associated bone disorders, where patients can differ substantially in bone remodelling activity, inflammatory status, bone formation capacity, osteoclast activity, and capacity for mechanoadaptation. A better understanding of these differences could support more personalised strategies for osteoporosis research and fracture prevention.

Building on the dynamic bone organoid culture platform developed in the Laboratory for Bone Biomechanics at ETH Zurich, this PhD project will contribute to the fracture prevention component by developing advanced patient-derived organoids for invitro osteoporosis research. The doctoral researcher will establish workflows to 3D patient-derived mesenchymal stromal cells, guide their osteogenic differentiation under dynamic mechanical stimulation, and coculture with peripheral blood mononuclear cells. These models will be used to study osteoporosis-related bone remodelling, immune-bone interactions, donor-specific osteoporotic phenotypes, and mineralisation dynamics, including the influence of age-related comorbidities on bone remodelling.

Biological readouts from the organoids will contribute to predictive modelling frameworks for bone remodelling trajectories and fracture risk, supporting the advancement of human-relevant in vitro models for precision musculoskeletal care.

The PhD candidate will interact closely with engineers, clinicians, biologists, computational researchers, to generate robust biological datasets for personalised modelling of bone remodelling and fracture prevention.

Some key components in the work are:

• Development of patient-derived organoids for in vitro osteoporosis research.
• Integration of peripheral blood mononuclear cells into mature bone organoids to model immune-bone interactions, monocyte-derived osteoclast activity, inflammation, and bone remodelling.
• Investigation of donor-specific differences and mineralisation dynamics associated with age, sex, and relevant comorbidities.
• Characterisation of osteoporosis-related organoid phenotypes using molecular, biochemical, histological, imaging, and microscopy-based techniques.

Applicants should hold an MSc degree in biomedical engineering, or a related discipline. After successful completion of studies, the PhD degree will be awarded by ETH Zurich.

The candidate should have previous experience in tissue engineering and mammalian cell culture. Experience with 3D cell culture, organoids, bone or musculoskeletal research, bioreactor-based culture systems, or mechanical stimulation of tissues would be advantageous. Experience with human primary cells, mesenchymal stromal cells, peripheral blood mononuclear cells, osteoclast differentiation, immune cell assays, or inflammatory signalling would be considered a strong advantage.

Experience in molecular, histological, imaging, and biochemical techniques, such as immunostaining, microscopy, gene expression analysis, cytokine profiling, mineralisation assays, or osteoclast activity assays. Experience with computed tomography, image analysis, Python-based data analysis, or quantitative data analysis would be an additional asset.

Candidates should be highly motivated, have a strong interest in skeletal research and precision medicine, and be resilient in addressing experimental challenges. They should be able to work on complex research topics with increasing independence, engage constructively with supervisors and collaborators, and incorporate feedback in a thoughtful and productive manner. Applicants must be proficient in written and spoken English, and familiarity with a cross-cultural and interdisciplinary research environment would be advantageous.

• Accredited with 5 Tripartite Standards by Tripartite Alliance for Fair & Progressive Employment Practices (TAFEP) Singapore.
• A diverse workplace with 32 nationalities, offering ample opportunities for mutual learning.
• Positive and inclusive working environment.
• 25 days of annual leave for fixed-term contracts.
• 1 day of Birthday Leave.
• Annual dental benefits.
• Committed to being a supportive employer as you prioritize your physical and mental wellness.
• Comprehensive healthcare insurance coverage.
• Flexible hybrid work arrangement (up to 2 days per week from home).
• Abundant networking opportunities across various disciplines.
• Accredited with NS mark certification.

In line with our values, ETH Zurich encourages an inclusive culture. We promote equality of opportunity, value diversity and nurture a working and learning environment in which the rights and dignity of all our staff and students are respected. Visit our Equal Opportunities and Diversity website to find out how we ensure a fair and open environment that allows everyone to grow and flourish. Sustainability is a core value for us – we are consistently working towards a climate-neutral future.

We look forward to receiving your online application with the following documents:

• A cover letter with a specific statement of your motivation for the project.
• Your CV including the name and contact information of 2 academic references.
• A copy of your university transcripts as PDFs.

Further information